We propose an interdisciplinary program of study which focuses on the cell surface of a wide variety of normal and malignant cell types. Toward this end we intend to integrate the approaches of ultrastructure, biochemistry, and biophysics. We will investigate the distribution and mobility of ionogenic-, lectin-, and immuno-specific sites on the cell surface. The degree of mobility of such cell surface sites will be studied with regard to cell function, to cell surface topography, to intramembrane particles and structure of the plasma membrane, to various cytoplasmic-plasma membrane interactions, and to cellular bioenergetics. Mobility of cell surface receptors will be studied in reconstituted systems of plasma membrane and cytoplasmic components. Plasma membrane biogenesis and turnover will be studied in synchronized and non- synchronized cell cultures and in cells undergoing hormonally-induced cilia formation. Correlations between membrane biogenesis and turnover, various cell surface binding sites, and the appearance of cellular microexudate or shed-plasma membrane components appearing in culture media, will be ascertained. We will investigate the ability of cultured cells to interact with one another through cell-cell contacts and junctions and during the development of such contacts. The dynamics of cell surface microextensions and retractions, the distributional changes of specialized surface receptors, and the alterations in electrotonic coupling, membrane resistance and transmembrane potential, will be monitored during the biogenesis of cell-cell contacts and junctions. We believe that our efforts will provide new, salient information on the architectural, functional and developmental interrelationships of the cell surface.